Solventless-mixing layering using a high shear mixer for preparing drug pellets: A feasibility study using acetaminophen

Our aim was to investigate the feasibility of mechanical-mixing layering using a high shear mixer, which can produce drug pellets by simply mixing drug crystals and inactive seed particles without the need for solvents or binders. Acetaminophen crystals and microcrystalline cellulose spheres were mechanically mixed using various impeller speeds and the resulting composite particles were characterized. Acetaminophen particles were separated from the spheres using a low impeller speed and deposited on the surface of the spheres at a higher impeller speed.

Highlights

• Drug layering can be achieved by solventless mixing using a high shear mixer.

• Drug pellets were produced by simply mixing drug crystals and core particles.

• The layering of drug crystals is due to the pulverization of those during mixing

The diameter of the acetaminophen crystals in the composite particles decreased as the impeller speed increased, due to increased collision impact between the spheres. The correlation between drug content and drug particle diameter in the composites indicates that acetaminophen particles were layered on the cellulose spheres due to their pulverization during the mixing treatment. We examined additional mixing treatments to enhance drug loading: after mechanically mixing acetaminophen crystals and cellulose spheres, fresh acetaminophen crystals were added and mechanically mixed with the composite particles. Additional mixing increased the loading of acetaminophen particles without lowering the layering efficiency. In conclusion, mechanical-mixing layering can be accomplished using a high shear mixer. Continue on pellet feasibility study using acetaminophen

Keita Kondo, Mizuki Kato, Toshiyuki Niwa,
Solventless-mixing layering using a high shear mixer for preparing drug pellets: A feasibility study using acetaminophen,
Advanced Powder Technology, 2021, ISSN 0921-8831,
https://doi.org/10.1016/j.apt.2021.08.016.